New Piperazine Derivatives of 6-Acetyl-7-hydroxy-4-methylcoumarin as 5-HT1A Receptor Agents. 2023

Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.

A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT1A and 5-HT2A receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (4) and 6-acetyl-7-{4-[4-(2-chlorophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (7) exhibited excellent activity for 5-HT1A receptors with Ki values 0.78 (0.4-1.4) nM and 0.57 (0.2-1.3) nM, respectively, comparable to the Ki values of 8-OH-DPAT (0.25 (0.097-0.66) nM). The equilibrium dissociation constant values of the tested compounds showed differential intrinsic activities of the agonist and antagonist modes.

UI MeSH Term Description Entries
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D006571 Heterocyclic Compounds Cyclic compounds that include atoms other than carbon in their ring structure. Heterocyclic Compound,Compound, Heterocyclic,Compounds, Heterocyclic
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D044263 Receptors, Serotonin, 5-HT1 A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels. Serotonin 5-HT1 Receptor,Serotonin Receptors, 5-HT1,5-HT1 Receptor,5-HT1 Receptors,Serotonin 5-HT1 Receptors,Serotonin, 5-HT1 Receptors,5 HT1 Receptor,5 HT1 Receptors,5-HT1 Receptor, Serotonin,5-HT1 Receptors Serotonin,5-HT1 Receptors, Serotonin,5-HT1 Serotonin Receptors,Receptor, 5-HT1,Receptor, Serotonin 5-HT1,Receptors Serotonin, 5-HT1,Receptors, 5-HT1,Receptors, 5-HT1 Serotonin,Receptors, Serotonin 5-HT1,Serotonin 5 HT1 Receptor,Serotonin 5 HT1 Receptors,Serotonin Receptors, 5 HT1,Serotonin, 5 HT1 Receptors
D044282 Receptor, Serotonin, 5-HT1A A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION. Serotonin 1A Receptor,5-HT(1A) Receptor,5-HT1A Receptor,5-Hydroxytryptamine 1A Receptor,5-Hydroxytryptamine 1A Receptors,Receptor, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5-HT1A,Serotonin, 5-HT1a Receptor,1A Receptor, 5-Hydroxytryptamine,1A Receptors, 5-Hydroxytryptamine,5 HT1A Receptor,5 Hydroxytryptamine 1A Receptor,5 Hydroxytryptamine 1A Receptors,5-HT1A Serotonin Receptor,5-HT1a Receptor Serotonin,Receptor Serotonin, 5-HT1a,Receptor, 5 Hydroxytryptamine 1A,Receptor, 5-HT1A,Receptor, 5-HT1A Serotonin,Receptor, Serotonin 1A,Receptors, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5 HT1A,Serotonin, 5 HT1a Receptor
D044402 Receptor, Serotonin, 5-HT2A A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD. Serotonin 2A Receptor,5-HT(2A) Receptor,5-HT2A Receptor,Receptor, Serotonin 2A,Serotonin 2A Receptors,5 HT2A Receptor,Receptor, 5-HT2A,Receptors, Serotonin 2A

Related Publications

Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
September 2017, European journal of medicinal chemistry,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
April 2015, Journal of inorganic biochemistry,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
December 2022, Chemical biology & drug design,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
January 1992, Progress in neuro-psychopharmacology & biological psychiatry,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
April 1994, Archiv der Pharmazie,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
February 2016, Marine environmental research,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
March 2000, Bioorganic & medicinal chemistry,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
January 2016, Pharmaceutical biology,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
January 2020, Current organic synthesis,
Kinga Ostrowska, and Anna Leśniak, and Weronika Gryczka, and Łukasz Dobrzycki, and Magdalena Bujalska-Zadrożny, and Bartosz Trzaskowski
April 1971, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Copied contents to your clipboard!